Frequency Therapeutics — Hearing Loss Regeneration

Discussion in 'Research News' started by RB2014, Dec 8, 2016.

    1. Selah1281

      Selah1281 Member Benefactor

      Location:
      Bustown, OH10
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Unknown
      Sorry I misread what you said.
      Here it is from @serendipity1996 above.
       
      • Like Like x 1
    2. patorjk

      patorjk Member

      Tinnitus Since:
      2008
      Cause of Tinnitus:
      Several reasons
      You're talking about the stock, right? I had a feeling there would be a post-presentation bump, though I didn't think it'd be as big as it is. They have 3 more presentations in the next 30 days, so I imagine the stock is going to stay high.

      However, after their October presentation, it seems like there's going to be a drought of new information. I'm not sure what they have planned for the time period between November and April 2021, but they're definitely going to do something (interim results? new study announcement? new hydrogel?), it'd be unlike them to just go quiet.
       
    3. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      It definitely seems like doubling is more accurate unless "acoustic energy" is what he means by "ability to hear" but that's not a metric I have really seen used.
       
    4. Danad

      Danad Member Benefactor

      Tinnitus Since:
      11/2017
      Cause of Tinnitus:
      Jet Engines, Concert
      Here are 2 adjacent tones at 8000Hz with a 15 dB difference (one subject was tested with that difference from baseline).

      Be sure to turn system volume down before playing since the 2nd tone is much louder.

      My informed albeit unscientific opinion is that gaining 10-15 dB of hearing sensitivity in the frequencies of one's tinnitus will be a game changer.
       

      Attached Files:

      • Agree Agree x 3
      • Helpful Helpful x 1
    5. Selah1281

      Selah1281 Member Benefactor

      Location:
      Bustown, OH10
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Unknown
      https://jlaudio.zendesk.com/hc/en-us/articles/217201737-Doubling-Power-vs-Doubling-Output

      “A change of 3 dB is accepted as the smallest difference in level that is easily heard by most listeners listening to speech or music. It is a slight increase or decrease in volume.”

      Yeah perhaps he was misquoted, misspoke or he was trying to come at it from a different angle like this to make it sound more substantial in a way (not to say it wouldn’t be substantial to say doubled).
       
      • Agree Agree x 1
    6. Selah1281

      Selah1281 Member Benefactor

      Location:
      Bustown, OH10
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Unknown
      He probably wasn’t misquoted since he said tripled twice in the set of quotes from the article.
       
    7. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Right, it seems unnecessary. Double is pretty substantial.
       
    8. tomytl
      Grumpy

      tomytl Member Benefactor

      Tinnitus Since:
      10 Years
      Cause of Tinnitus:
      unknown
      FX-322 is injected into the middle ear, it enters the inner ear „liquid“ through the round window membrane.

      What is the reason that the whole inner ear perilymph isn‘t mixed with FX-322?

      Is the perilymph kind of viscous or will the liquid not move or circulate in a way?
       
    9. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      The perilymph's current is actually stimulated from the tip of the apex (helicotrema) to the base.

      "The mechanical vibrations of the stapes footplate at the oval window creates pressure waves in the perilymph of the scala vestibuli of the cochlea. These waves move around the tip of the cochlea through the helicotrema into the scala tympani and dissipate as they hit the round window."

      This isn't the route of IT drugs traveling from the round window through the ear but is where drugs end up and are eliminated (but is useful for sampling drug concentrations just as sampling urine can tell you how much drug went through a kidney).
       
      • Helpful Helpful x 1
    10. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      I found this which I think explains Frequency Therapeutics' multiple dosing rationale rather than increasing concentration:

      "Bird and colleagues noted a large inter-variability in perilymph concentrations between patients after intratympanic administration of a methylprednisolone or a dexamethasone solution, providing a rationale for the reported variable clinical successes. Several factors can positively influence the clinical outcome. More than the absolute dose given at each administration or the total cumulative dose, the number of injections and the interval between them emerge as better predictors of a positive clinical outcome."

      From: https://www.frontiersin.org/articles/10.3389/fncel.2019.00238/full

      It also explains the variability if IT Dexamethasone. My guess based on this is that the patients who received 4 injections will have a much more pronounced result than the others.

      Polarity is also a factor and it seems that some formulations of Dexamethasone are better than others but it seems lile frequency of dosing may actually be the biggest factor (but not the only one).
       
      • Informative Informative x 4
      • Helpful Helpful x 3
      • Like Like x 1
    11. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      Some things that you should look at from this trial:

      - Half of the patients got placebo and half FX-322

      - Out of the half who got the drug half got the high dose and half got the low dose. Data suggests that the participants getting the high dose did gain improvements (hence Frequency Therapeutics has chosen to use the big dose in future trials)

      - Those taking the big dose all had improvement of some kind. It is just the case that there were some who had an improvement which was not deemed statistically significant (hence how one subject had a 71% word score improvement but this was not deemed statistically significant) and some did not have a dB improvement.

      - This was a safety dose trial only. Hence the trial results were a secondary and also extra measure Frequency Therapeutics added to this trial.
       
      • Like Like x 5
      • Agree Agree x 2
    12. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      It looks like all but one of the moderate group kept most of their word score improvements, though it looks like for some they had to "scale up" a 25 word test because the one year retesting was done at different centers than the original testing (I wonder how much this is a factor). One person did decline and I wonder if there was something that happened within the year to instigate this.

      It also looks like of the 4 who had the 10 dB improvements, after 1-2 years, 2 remained the same, someone gained an additional 5 dB and someone declined.

      I really want to know more about the person who declined because they saw improvements initially and I wonder if they were less careful after or had some other incident in the year or an immune state that made them more prone to injury.

      Phase 2a should be useful in sussing things like this out because the sample size is so much larger.

      But it looks like most of the moderate hearing loss people kept most of their improvements. I wonder if repeat dosing (and also repeat courses every few years) may be needed in some people which presumably would be doable since the support cells are not depleted.
       
      • Agree Agree x 2
    13. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      This is why I think that the comments he made in this article are somewhat loaded and also biased. When you go through the claims he has made, many of them do not even comply with the scientific facts or scientific standards. Furthermore I thought that nearly every comment this doctor made on Frequency Therapeutics and FX-322 was negative, appeared to be critical and also actually ignored the scientific facts and outcomes as well.

      You've already referred to the dB improvement statement, which was one example.

      However you also have to look at the fact that this guy has said that they only got hair cells growing in mice and then acknowledges a dB increase was achieved in people as well. Yet interestingly he provided no supporting information to explain why there could have been a dB increase without hair cell regrowth. Furthermore it is interesting that he ignores other facts and achievements from the inaugural trial like the improvement in word scores. Something tells me that this omission was on purpose because acknowledging it would flat out contradict the other criticisms he had made.

      In fact it is incredibly interesting that he fails to back up nearly all his negative/dismissive claims about the work of Frequency Therapeutics with any evidence whatsoever. Even when he used evidence to support these negative/critical claims he was making, the evidence used seemed to reject the widely accepted standards.

      This article and this doctor's comments lead me to the belief that this was possibly produced to criticise FX-322 and Frequency Therapeutics to serve the interests or purpose of another organisation. One can liken this to those stories on a topic or an issue in magazines and papers which are actually thinly veiled advertisements for a product/service/event being provided by an organisation.

      It simply doesn't make sense that a research doc could ignore so many obvious and basic scientific rules and facts when making his statements. I get the feeling this is wilful and also maybe some strange ulterior motive might be coming into play.
       
      • Agree Agree x 2
      • Like Like x 1
    14. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      It was strange.

      There were a couple of statements in that article that were blatantly false such as 10 dB being suggested to be within the retest of error and FX-322 not shown to regrow hair cells in adult mammals (which it did in both adult rodents and explant studies).

      I honestly think it was the writer looking for doctors willing to say negative statements to appear unbiased but it isn't completely unheard of for there to be "hit pieces" against publicly traded companies. This happened a lot with Sarepta, a biotech I invested in years ago.
       
      • Like Like x 1
    15. Selah1281

      Selah1281 Member Benefactor

      Location:
      Bustown, OH10
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Unknown
      He’s a pioneering surgeon in cochlear implants. He also appears to have a vested interest in the technology if he still sits on the Scientific Advisory Board for Iotamotion.

      https://www.hearingreview.com/heari...announces-formation-scientific-advisory-board
       
      • Informative Informative x 1
    16. Selah1281

      Selah1281 Member Benefactor

      Location:
      Bustown, OH10
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Unknown
      And the article itself says Cheng is on the Scientific Advisory Board for Decibel Therapeutics.
       
    17. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      My own theory is that if you had mild hearing loss, you are less likely to have widespread damage so your 8000 Hz may not be affected but (especially if noise induced which they selected for) you may have a notch or two in lower frequencies.

      I really wish we could see the audiograms of the patients, that would be so helpful.
       
      • Agree Agree x 4
      • Like Like x 1
    18. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      This article's absolutely a hit job on FX-322 and also Frequency Therapeutics. I remember our English teacher going through these type of articles and their purpose(s) at school. She said the whole idea of them is to use facts like statistical data and comments from 'experts' to make it look like they've written a believable, legitimate and factual article.

      Yet what they actually do is manipulate these facts and comments and 'report' them in a disingenuous way to make the readers form the opinion or conclusion on the topic that the author and/or article's sponsor wants them to form.

      We have already alluded to the article's disingenuous and erroneous reporting of stats relating to FX-322 trials. Yet have a look at the doctors who got asked to comment. A cynical individual might actually think that they have deliberately chosen them. :)? Interestingly they all work and undertake research in the hearing field and medicine like OTO-413 or FX-322 achieving positive outcomes would probably have an adverse impact on their work/research.

      When you take the fabric of the article apart, there are clear indications that the article has been crafted to negatively reflect on FX-322 and surely there has to be an underlying reason for this.

      I'm telling you now, I'm feeling that there is going to be a lot of attempts at smearing Frequency Therapeutics in the next few years from from various groups within the hearing sector.

      I think that Frequency Therapeutics achievements thus far have demonstrated FX-322 is a legit medicine and therefore it will be a disruptor to the industry as it currently stands. Also their methodology is excellent and actually at this stage seems very hard to criticise.

      It seems Frequency Therapeutic's work to date has upset a lot of people who fall in the status quo and they may actually be starting to demonstrate their displeasure and using Frequency Therapeutics as the punching bag because they are at the front and they are the face of this.
       
      • Agree Agree x 2
      • Like Like x 1
    19. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      Thanks. I knew that name had popped up somewhere before. I had an inkling he was working more widely than just being a doctor.

      I might be basically seen as a cynic, however I have a pretty good read on things when it seems that someone might have an underlying motive or when things don't seem 100% legit. This doctor's comments definitely fell into both of these categories
       
    20. vttbx

      vttbx Member Benefactor

      Tinnitus Since:
      01/2001
      I'm curious if improvement above 8 kHz is somehow more difficult to achieve than below 8 kHz with FX-322. Granted, I'd be happy to take either at this point, but my concern is above 8 kHz.
       
    21. d'Wooluf

      d'Wooluf Member

      Tinnitus Since:
      2010
      Cause of Tinnitus:
      unknown
      I'd hold off before turning a difference of opinion into evidence of malice. Anyway, I found this. Agree or not, the guy's statement isn't out of the ballpark.

      https://www.bc-legal.co.uk/bc-disea...a-basis-for-nihl-claims-handling-schemes.html.

      The central tool in diagnosis is the audiogram. Audiograms are taken in steps of 5 dB at each frequency. They are variable and not generally exactly repeatable. Where 2 audiograms taken at about the same time vary, the results where there is variation may reasonably be averaged if the difference is not more than 10 dB. Up to 10 dB is therefore an acceptable margin of error”.
       
    22. Billy_Shears

      Billy_Shears Member Benefactor

      Location:
      Knoxville, Tennessee
      Tinnitus Since:
      2010
      Cause of Tinnitus:
      Pink Floyd
      It is interesting that you point out the "hearing sector". The hearing aid industry throughout the world is huge and has enjoyed for many years as an industry monopoly on providing 'patients' with an answer to getting on with their lives. The Audiologist is the middle man or woman you go to in order to purchase a $6K hearing aid after undergoing an audiogram. Frequency Therapeutics is delivering a lasting, natural solid solution in the advent of FX-322 and, therefore, threatens an industry that has long dominated the 'hearing sector'.

      Hearing aids will still be in demand for many with severe-profound hearing loss but the sector will receive a much smaller slice of the pie. The economics of it all, it seems, has stirred up a hornet's nest. I could sense it in the reply from my audiologist when I mentioned FX-322 - "trials have been going on since the mid 90's"
       
    23. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      Nobody can definitively say because there is no data published as of yet on above 8 kHz.

      However there are a number of logical assumptions which can be made based off of the information that we have from both the inaugural trial and also with what we know about how a cochlear functions.

      I have tried to logically and sequentially order these:

      - The very high frequencies are at the outside of the cochlear (eg: 20000 Hz) and the lower frequencies are furthest in (eg: 250 Hz).

      - Based upon the layout of a cochlear, the medicine should hit the very high frequencies first, as they are closer to where the medicine is injected and treat these much more easily than the lower frequencies.

      - In the phase1/2 trial, the only dB improvement noted was at 8000 Hz.

      This is because the trial's audiogram testing ceiling was 8000 Hz and as a result nothing was tested above this.

      - However the word recognition scores also improved in a large number of participants who received FX-322.

      Some of these improvements were deemed to be not statistically significant according to the trial reporting criteria, however many felt that they were significant from a practical perspective.

      - Based off of the word recognition score improvements, it is assumed a benefit was obtained in the very high frequencies.

      This conclusion could be reasonably made because it is seemingly now understood that the very high frequencies (those above 8000 Hz) assist with word and sound clarity.

      - Therefore based off of the information obtained from the phase1/2 trial, it is highly likely that there was improvement in the very high frequencies.

      We can reasonably assume this fact based on:

      > The improvement in word recognition scores across a very high percentage of those given FX-322.

      > The fact that the medicine would have had to hit the areas of the cochlear where frequencies from 20000 Hz to 8000 Hz are in order to reaching 8000 Hz which it treated favourably.

      Therefore the evidence and information we have about the performance and benefit provided by FX-322 to date indicates that the medicine is highly likely to provide good benefit with the very high frequencies above 8000 Hz. We will need to wait for the official trial data to have definitive evidence either way, however it is looking very promising.
       
      • Agree Agree x 2
      • Like Like x 1
    24. tomytl
      Grumpy

      tomytl Member Benefactor

      Tinnitus Since:
      10 Years
      Cause of Tinnitus:
      unknown
      Yes, he is a specialist @ Stanford.

      I guess it‘s normal that there are always other opinions, especially if the dataset leaves some space for interpretation.

      I remember when Marcelo Rivolta published some findings of stem cell treatment for hearing regeneration, it was also criticized by a top researcher of Stanford.

      Yet now Rivolta has got funding and established Rinri Therapeutics.

      So there is probably some competition between the labs, but it isn‘t necessarily the case. At this stage it‘s rocket science with trial and error with many uncertainties.

      I also remember a researcher offering a contrary opinion in regards to the Novartis Atoh1 trial. He told me that nobody else in the field could replicate their results in the lab, so he was very skeptical... same guy is also cautious about FX-322, but he welcomes this step even though he is also involved in other companies who are working on hair cell regeneration.

      I just pray that the FX-322 Phase 2a results show us further positive trends and that everything is fast-tracked.
       
      • Agree Agree x 2
      • Like Like x 1
    25. KotaDomowa
      Dreaming

      KotaDomowa Member

      Location:
      Poland
      Tinnitus Since:
      Februar 2018
      Cause of Tinnitus:
      Unknown
      Hmm... I can't hear anything above 16 kHz in my right ear. Absolutely zero. But the otoemissions are within the normal range.

      Do you think FX-322 can help me?
       
    26. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      Are we supposed to be able to hear above that frequency? Don't we lose those frequencies due to the normal aging process.
       
      • Agree Agree x 2
    27. KotaDomowa
      Dreaming

      KotaDomowa Member

      Location:
      Poland
      Tinnitus Since:
      Februar 2018
      Cause of Tinnitus:
      Unknown
      During the examination, I was 22 years old. I can hear in my left ear up to 20 kHz. And the tinnitus is mostly in my right ear.
       
    28. AUTHOR
      AUTHOR
      RB2014
      Confused

      RB2014 Member Benefactor

      Location:
      US
      Tinnitus Since:
      12/2014 became noticable
      Cause of Tinnitus:
      Loss of hearing and then stress and anxiety
      Yes, we do lose those frequencies as we get older. Some people lose them faster than others.

      Read what tommyd87 wrote in the post above. His reasoning is sound and right on target. At this point we think there is a good chance that 8k frequencies improved and that frequencies above 8k improved as well.

      I wonder if some of these guys writing negative comments are shorting the stock.....

      I'm still staying cautiously optimistic until the data on the next trials can be obtained. We are making a lot of assumptions that could go either way.
       
    29. weab00

      weab00 Member Benefactor

      Tinnitus Since:
      04/2019
      Cause of Tinnitus:
      Headphone use/concerts, neck whiplash
      What do you guys think of this comment on /r/tinnitusresearch?

      "I am an audiologist. 5-10 dB HL difference on an audiogram at one frequency (high or low) in one ear is not significant. When you test hearing all day every day you see it happening often. I would not reprogram a hearing aid based on that difference.... Now, even though 5-10 dB HL is not significant, I would reprogram a hearing aid if there were three or more frequencies that changed by 10dB HL and the patient says their CLEAN hearing aid sounds soft/loud.

      I also would not get excited about their word recognition improving from 20% to 40% for one person. Their audiogram did not significantly improve, but their word scores did? There are several reasons for that improvement. For example how the BRAIN (not the cochlea) is processing that sound/word heard. The brain is affected by familiarity with a test, attention, fatigue, mood...

      Side note: If the results were actually significant, that would be super exciting, but they would still have a long way to go. My next question would be... is this change temporary? Will they need to get this treatment once every 3, 6, 12 months?"
       
    30. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Otoacoustic emissions cover from about 500 Hz to around 8000 Hz (or slightly less). Doesn't tell you much in your case. If your tinnitus is caused by cochlear hair cell loss in the ultra high frequency range, then you might be an ideal candidate.
       
      • Agree Agree x 1
      • Informative Informative x 1

Share This Page

Loading...